ABSTRACT
OBJECTIVE To study the protective effects of ligustrazine-scutellarein twin drug ST-11 on rat adrenal medullary pheochromocytoma PC12 cell injury induced by oxygen-glucose deprivation/reperfusion （OGD/R） and its mechanism. METHODS PC12 cells were divided into blank group， model group， nimodipine group （positive control， 5 μmol/L） and different concentration groups of ST-11 （5， 10， 20 μmol/L）. After 24 hours of pre-administration intervention， all the other groups except the blank group were cultured in glucose-free DMEM culture medium containing 10 mmol/L Na2S2O4 for 4 hours with glucose deficiency and hypoxia. After 4 hours of glucose and oxygen re-introduction， the survival rate of cells in each group， the contents of lactate dehydrogenase （LDH）， catalase （CAT）， glutathione （GSH）， malondialdehyde （MDA） and superoxide dismutase （SOD） in cell supernatant， apoptosis rate， the levels of reactive oxygen species （ROS） and mitochondrial membrane potential （MMP）， the protein expressions of B-cell lymphoma 2 related X protein （Bax）， B-cell lymphoma 2 （Bcl-2） and caspase-3 were all detected in each group. RESULTS Compared with blank group， the cell survival rate， the contents of CAT， GSH and SOD in cell supernatant， MMP level， relative expression of Bcl-2 and Bcl-2/Bax ratio in model group decreased significantly （P＜0.05）， while the contents of LDH and MDA， ROS level， apoptosis rate， relative expressions of Bax and caspase-3 were significantly increased （P＜0.05）. Compared with model group， above indexes of ST-11 groups （except for the protein expression of caspase-3 in 5 μmol/L ST-11 group） were reversed signifi-cantly （P＜0.05）. CONCLUSIONS ST-11 has a certain protec-tive effect on OGD/R-injured PC12 cells， and its effects may be related to reduction of oxidative stress and inhibition of cell apoptosis.
ABSTRACT
OBJECTIVE To study the protective effects of twin drugs of tetramethylpyrazine-scutellarein （TMSC4） on cerebral ischemia-reperfusion injury （CIRI） model rats and its mechanism. METHODS One hundred and five SD rats were randomly divided into sham operation group， model group， scutellarein group （0.7 mmol/kg）， tetramethylpyrazine group （0.7 mmol/kg）， and TMSC4 low-dose， medium-dose and high-dose groups （0.35， 0.7， 1.4 mmol/kg）， with 15 rats in each group. Sham operation group and model group were given constant volume of normal saline intragastrically， and other groups were given relevant drug intragastrically， once a day， for consecutive 14 d. Except for sham operation group， all other groups were treated to establish the CIRI model using the thread occlusion method. After 2 hours of ischemia and 22 hours of reperfusion， the brain index and brain water content of the rats were measured. Serum levels of interleukin 1β （IL-1β）， IL-6 and tumor necrosis factor α （TNF-α）， the levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px） and catalase （CAT） in brain tissues， the situation of neuronal cell apoptosis， and the protein expressions of B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax） and cleaved-caspase-3 were evaluated. RESULTS Compared with sham operation group， the brain index， brain water content， the serum levels of IL-1β， IL-6 and TNF-α， the levels of MDA in brain tissues， the brain cell apoptosis and the protein expressions of Bax and cleaved-caspase-3 in model group were significantly increased （P＜0.05）； the levels of SOD， GSH- Px and CAT and the protein expression of Bcl-2 in brain tissues were significantly decreased （P＜0.05）. Compared with model group， the above indexes of rats were reversed significantly in administration groups （P＜0.05）， while the reverse effects of TMSC4 medium-dose and high-dose groups were significantly better than those of scutellarein group and tetramethylpyrazine group （P＜0.05）. CONCLUSIONS TMSC4 has a certain protective effect in CIRI model rats， the mechanism of which may be related to relieving inflammatory reaction and oxidative stress， inhibiting cell apoptosis.